CN111494649A - Graphene quantum dot and gadolinium ion chelate magnetic resonance contrast agent and preparation method thereof - Google Patents
Graphene quantum dot and gadolinium ion chelate magnetic resonance contrast agent and preparation method thereof Download PDFInfo
- Publication number
- CN111494649A CN111494649A CN201910095524.6A CN201910095524A CN111494649A CN 111494649 A CN111494649 A CN 111494649A CN 201910095524 A CN201910095524 A CN 201910095524A CN 111494649 A CN111494649 A CN 111494649A
- Authority
- CN
- China
- Prior art keywords
- graphene quantum
- quantum dot
- chelate
- gadolinium ion
- gadolinium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 229910021389 graphene Inorganic materials 0.000 title claims abstract description 64
- 239000002096 quantum dot Substances 0.000 title claims abstract description 36
- 239000013522 chelant Substances 0.000 title claims abstract description 35
- RJOJUSXNYCILHH-UHFFFAOYSA-N gadolinium(3+) Chemical compound [Gd+3] RJOJUSXNYCILHH-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 31
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 230000009920 chelation Effects 0.000 claims abstract description 9
- 230000001590 oxidative effect Effects 0.000 claims abstract description 8
- 239000002086 nanomaterial Substances 0.000 claims abstract description 6
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 239000002872 contrast media Substances 0.000 claims description 19
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 238000001035 drying Methods 0.000 claims description 11
- MEANOSLIBWSCIT-UHFFFAOYSA-K gadolinium trichloride Chemical compound Cl[Gd](Cl)Cl MEANOSLIBWSCIT-UHFFFAOYSA-K 0.000 claims description 11
- 238000010992 reflux Methods 0.000 claims description 10
- 238000000799 fluorescence microscopy Methods 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 7
- 229910021641 deionized water Inorganic materials 0.000 claims description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 238000005303 weighing Methods 0.000 claims description 5
- 238000000502 dialysis Methods 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- -1 gadolinium ions Chemical class 0.000 claims description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 3
- 238000001027 hydrothermal synthesis Methods 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000000967 suction filtration Methods 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 238000005194 fractionation Methods 0.000 claims description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 2
- 238000009210 therapy by ultrasound Methods 0.000 claims description 2
- 238000009777 vacuum freeze-drying Methods 0.000 claims description 2
- 239000012216 imaging agent Substances 0.000 claims 1
- 231100000053 low toxicity Toxicity 0.000 abstract description 6
- 239000008055 phosphate buffer solution Substances 0.000 abstract description 6
- 238000012360 testing method Methods 0.000 abstract description 6
- 239000007864 aqueous solution Substances 0.000 abstract description 4
- 239000001963 growth medium Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 19
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical group [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 15
- 238000002595 magnetic resonance imaging Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 230000006872 improvement Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 230000005284 excitation Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 239000002616 MRI contrast agent Substances 0.000 description 2
- 208000003510 Nephrogenic Fibrosing Dermopathy Diseases 0.000 description 2
- 206010067467 Nephrogenic systemic fibrosis Diseases 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- ZPDFIIGFYAHNSK-UHFFFAOYSA-K gadobutrol Chemical compound [Gd+3].OCC(O)C(CO)N1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 ZPDFIIGFYAHNSK-UHFFFAOYSA-K 0.000 description 1
- GFSTXYOTEVLASN-UHFFFAOYSA-K gadoteric acid Chemical compound [Gd+3].OC(=O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 GFSTXYOTEVLASN-UHFFFAOYSA-K 0.000 description 1
- 229960003823 gadoteric acid Drugs 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960003330 pentetic acid Drugs 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 231100000857 poor renal function Toxicity 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000004729 solvothermal method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/65—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing carbon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
- C01B32/182—Graphene
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
- C01B32/182—Graphene
- C01B32/198—Graphene oxide
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
- C09K11/025—Use of particular materials as binders, particle coatings or suspension media therefor non-luminescent particle coatings or suspension media
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y25/00—Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/01—Particle morphology depicted by an image
- C01P2004/04—Particle morphology depicted by an image obtained by TEM, STEM, STM or AFM
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/80—Particles consisting of a mixture of two or more inorganic phases
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2006/00—Physical properties of inorganic compounds
- C01P2006/60—Optical properties, e.g. expressed in CIELAB-values
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2006/00—Physical properties of inorganic compounds
- C01P2006/80—Compositional purity
- C01P2006/82—Compositional purity water content
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Materials Engineering (AREA)
- Inorganic Chemistry (AREA)
- Nanotechnology (AREA)
- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a graphene quantum dot and gadolinium ion chelate (Gd @ GQDs), belonging to the field of nano materials, wherein the graphene quantum dot and gadolinium ion chelate are nano materials, and the surfaces of the graphene quantum dot and gadolinium ion chelate are provided with hydrophilic groups; the preparation method comprises the steps of preparing graphene oxide by using a Hummers method, heating, oxidizing and purifying to obtain pure graphene quantum dots, and finally mixing the pure graphene quantum dots with Gd3+Chelation forms stable Gd @ GQDs. The Gd @ GQDs prepared by the method are easily dispersed in water, Phosphate Buffer Solution (PBS), biological culture medium and other aqueous solution systems; has good biocompatibility and low toxicity; in a 1.5T magnetic resonance test system, excellent T is shown1Weighted contrast performance of r1The relaxation rate is as high as 72mM‑1s‑1Compared with the prior commercial T1Weighting r of magnetic resonance contrast agent Gd-DTPA1The value is twenty times higher.
Description
Technical Field
The invention relates to a graphene quantum dot and gadolinium ion chelate magnetic resonance contrast agent and a preparation method thereof, belonging to the technical field of new nano materials.
Background
Magnetic Resonance Imaging (MRI) is one of the most widely used diagnostic tools in clinical applications. MRI has many advantages, such as non-invasiveness, high spatial and temporal resolution, and good soft tissue contrast. Nevertheless, the inherent signal differences between tissues, particularly between diseased and normal tissues, are not as great. Therefore, the temperature of the molten metal is controlled,MRI contrast agents are typically injected prior to scanning to improve imaging quality. Classified according to the principle of action, MRI contrast agents can be classified as longitudinal relaxation contrast agents (T)1Contrast agents) and transverse relaxation contrast agents (T)2A contrast agent). Most commonly used T1The contrast agent is a gadolinium-based contrast agent, since Gd3+Can provide seven unpaired electrons, resulting in a higher longitudinal relaxation rate (r)1). However, free Gd3+Has high toxicity, Gd3+A rare disease known as Nephrogenic Systemic Fibrosis (NSF) can be induced in the body, and is especially fatal in patients with impaired renal function. To inhibit its toxicity, various ligands and Gd are generally used3+Complexing to free Gd3+The release is minimized. Examples include Gd-DTPA (DTPA-diethylenetriaminepentaacetic acid), gadoteric acid, Gd-DO3A butrol (DO3A-1,4, 7-tris (carboxymethyl) cyclododecane-10-azaacetamide), gadodiamine and the like. However, these gadolinium-based chelates are high in gadolinium content and practical amounts, still resulting in Gd3+Leakage in the body thus poses a biological safety problem. Therefore, there is an urgent need to develop a composition having extremely low Gd3+T with good content, good biological safety and high performance1The contrast agents are weighted.
The Graphene Quantum Dots (GQDs) are mainly formed by sp2The graphene sheet is a two-dimensional graphene sheet which is composed of hybridized carbon atoms, has the same lattice spacing as graphite, has the transverse dimension of less than 100nm and has less than 10 atomic layers. The GQDs not only have the excellent performances of graphene, such as large specific surface area, high electron mobility and good mechanical strength, but also have excellent fluorescence performance, light stability, low toxicity, good biocompatibility, easy surface modification and the like. Because of the excellent characteristics, GQDs have great application prospects in the fields of biomedical imaging, optical materials and devices, biosensing, environmental detection and the like, and especially provide a material basis for constructing a clinical application multi-mode imaging platform.
With the urgent need of early diagnosis and accurate treatment of serious diseases such as cancer, single diagnostic techniques such as MRI, fluorescence imaging and ultrasound imaging have not been able to meet the needs of people. Therefore, multimode imaging technology and materials thereof, which integrate multiple functions, are widely concerned and researched by researchers. Aiming at the problems, the invention invents GQDs and gadolinium ion chelates which have the functions of MRI and fluorescence imaging as medical developers.
Prior art related to the present invention: documents of complexes of carbon quantum dots and gadolinium as magnetic resonance contrast agents have been published in international academic journals Advanced Materials 2014,26, 6761-6766 and Advanced Materials2018, 1802748. The work is to utilize organic micromolecules to complex with gadolinium ions or utilize the existing commercial gadolinium-based contrast agent to synthesize a compound of a carbon quantum dot and gadolinium through a water/solvothermal method, and then the compound is used for magnetic resonance imaging. The method has the disadvantages that the cost of raw materials is high, the structure of the obtained compound of the carbon quantum dots and gadolinium is not clear, the gadolinium content and the using amount during contrast are high, and the later stage can cause great influence on organisms. More importantly, the longitudinal relaxation rate r of the contrast agent1Is much smaller than r of the contrast agent of the invention1Thus T thereof1The weighted contrast effect is far less than the patented technology.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a graphene quantum dot and gadolinium ion chelate which has good biocompatibility and low toxicity, can be applied to magnetic resonance imaging and fluorescence imaging, and has excellent T1Weighting contrast effects and high efficiency fluorescence function.
The invention also provides a preparation method and application of the graphene quantum dot and gadolinium ion chelate.
In order to achieve the purpose, the graphene quantum dot and gadolinium ion chelate are adopted, and the graphene quantum dot and gadolinium ion chelate are a nano material and have the characteristics of large specific surface area, stable optical property, hydrophilic groups on the surface and the like.
In addition, the invention also provides a preparation method of the graphene quantum dot and gadolinium ion chelate, graphene oxide is prepared by using a Hummers method, pure graphene quantum dots are obtained by heating and oxidizing, and finally, the pure graphene quantum dots and Gd are mixed3+And (4) chelating to form a stable graphene quantum dot and gadolinium ion chelate.
As an improvement, the method specifically comprises the following steps:
1) preparing graphene oxide by using a Hummers method;
2) weighing the prepared graphene oxide, dissolving the graphene oxide in deionized water, carrying out ultrasonic treatment, and adding a certain amount of strong oxidant for full dissolution;
3) adding 400-1000 mu L alkali compound into the solution, and then refluxing for 7-12h at 70-120 ℃;
4) after the reflux is finished, purifying and drying to obtain the graphene quantum dots, wherein the graphene quantum dots have the characteristics of two-dimensional regular morphology, uniform size, transverse size of 3-6nm, thickness of 1-2nm, non-excitation light dependent luminescence and the like;
5) preparing pure graphene quantum dots into a solution with a certain concentration, and then adding a certain amount of gadolinium chloride solution to perform chelation reaction under a certain condition;
6) and purifying and drying the solution after reaction to obtain the graphene quantum dot and gadolinium ion chelate.
As a modification, the ultrasonic power in the step 2) is 500-800W.
As a modification, the strong oxidant in the step 2) adopts one or more of potassium persulfate, hydrogen peroxide, concentrated sulfuric acid, concentrated nitric acid and hypochlorous acid.
As an improvement, the mass ratio of the graphene oxide to the strong oxidant in the step 2) is (1-3): (1000-3000); the mass ratio of the graphene oxide to the deionized water is (1-3): (1000-3000).
The alkaline compound in the step 3) is one or more of potassium hydroxide, sodium hydroxide, ammonia water, hydrazine hydrate, ethylenediamine and hydroxylamine.
As a modification, the purification in the step 4) and the step 6) is any one or more of suction filtration, chromatography, dialysis, filtration, extraction and distillation fractionation; the drying in the step 4) and the step 6) is any one or more of vacuum drying, freeze drying and high-temperature drying.
As an improvement, the concentration of the solution prepared by the graphene quantum dots in the step 5) is 0.05-0.4mg m L-1The concentration of the gadolinium chloride solution is 0.1-0.5mmol L-1。
As an improvement, the chelation reaction in the step 5) can be any one of conventional water bath heating, hydrothermal reaction, solution dialysis and normal temperature treatment, but the chelation time of the normal temperature treatment is relatively longer.
Finally, the invention also provides an application of the chelate or the graphene quantum dot and gadolinium ion chelate obtained by the preparation method as a medical image developer.
As an improvement, the medical image developer comprises a magnetic resonance imaging contrast agent and a developer for fluorescence imaging.
Compared with the prior art, the invention has the beneficial effects that:
1) the graphene quantum dot and gadolinium ion chelate (Gd @ GQDs) prepared by the method are nano materials, the surface of the graphene quantum dot and gadolinium ion chelate is provided with hydrophilic groups such as hydroxyl, carboxyl and amino, and the sample is uniform in size, has stable optical performance and is easy to perform surface modification.
2) The Gd @ GQDs prepared by the method are easily dispersed in water, Phosphate Buffer Solution (PBS), biological culture medium and other aqueous solution systems.
3) The cytotoxicity of Gd @ GQDs prepared by the method is tested by an MTT method, and the test result shows that the survival rate of cells is still maintained to be over 90 percent after MCF-7 and CHO cells are co-cultured with Gd @ GQDs with different concentrations and DMEM medium solutions for 24 hours, which indicates that the Gd @ GQDs prepared by the method have very low toxicity.
4) The Gd @ GQDs prepared by the method have excellent fluorescence performance, and the fluorescence of the Gd @ GQDs has the non-excitation light wavelength dependence of standard graphene quantum dots. The fluorescent material can show blue, green and red fluorescence when excited by ultraviolet light, blue light and green light respectively, and can be applied to a fluorescence imaging technology.
5) The Gd @ GQDs prepared by the invention shows excellent T in a 1.5T magnetic resonance testing system1Weighted contrast performance of r1The relaxation rate is as high as 72mM-1s-1Is a composite contrast agent r of carbon quantum dots and gadolinium reported in the above documents15-12 times of the prior commercial T1Weighting r of magnetic resonance contrast agent Gd-DTPA1The value (3.0 to 4.0 mM)-1s-1) More than twenty times of the total weight of the product. More importantly, in practical application, Gd in Gd @ GQDs3+The injection dosage of (A) is gadolinium-based T in the above-mentioned document1Contrast agents and general commercial gadolinium-based T1One fiftieth of the contrast agent. In addition, Gd in the Gd @ GQDs material of the invention3+Although only gadolinium-based T is present in the above-mentioned documents1Between one fourth and one third of the contrast agent, but still achieving a good magnetic resonance contrast, which makes Gd avoided from the source3+A large number of leakage hazards. Therefore, the Gd @ GQDs magnetic resonance contrast agent has good application prospect clinically.
Drawings
FIG. 1 is a transmission electron microscope image of Gd @ GQDs of the present invention;
FIG. 2 is a Fourier transform infrared spectrum of Gd @ GQDs prepared according to the present invention;
FIG. 3 shows the results of MTT cytotoxicity assay of Gd @ GQDs prepared according to the invention (Gd @ GQDs at different concentrations were co-cultured with CHO and MCF-7 cells for 24 h).
FIG. 4 shows an aqueous solution of Gd @ GQDs of the present invention prepared in a 1.5T magnetic resonance imaging system1And r2Relaxation Rate (R in the figure)2To fit the correlation coefficient).
FIG. 5 shows that the cells of Gd @ GQDs, gadolinium chloride, Gd-DTPA and MCF-7 prepared by the invention are co-cultured and then T is processed in a 1.5T magnetic resonance radiography system1The magnetic resonance image is weighted.
FIG. 6 shows fluorescence microscope images (scale: 50 μm) of Gd @ GQDs prepared according to the present invention for cell visualization, which are bright field (top left), blue fluorescence (top right), green fluorescence (bottom left), and red fluorescence (bottom right), in that order.
Detailed Description
The following examples are further illustrative of the present invention as to the technical content of the present invention, but the essence of the present invention is not limited to the following examples, and one of ordinary skill in the art can and should understand that any simple changes or substitutions based on the essence of the present invention should fall within the protection scope of the present invention.
Example 1
A preparation method of a graphene quantum dot and gadolinium ion chelate specifically comprises the following steps:
1) graphene oxide was prepared using Hummers method (this method is cited from the literature: ACS Nano,2010,4(8), 4806-;
2) weighing 20mg of the graphene oxide, dissolving the graphene oxide in 60g of deionized water, treating with the ultrasonic power of 500W, and then adding 60g of hydrogen peroxide for full dissolution;
3) adding 1000 mu L hydrazine hydrate solution into the solution, transferring the solution into a round-bottom flask, and refluxing for 8 hours in an oil bath at 100 ℃;
4) after the reflux reaction is finished, filtering and purifying the solution to remove large-block impurities, and then drying at high temperature (80 ℃) to obtain GQDs which have the characteristics of two-dimensional regular morphology, uniform size, transverse size of 3-6nm, thickness of 1-2nm, non-excitation light dependent luminescence and the like;
5) the GQDs prepared above was formulated to a concentration of 0.35mg m L-1Adding gadolinium chloride into the solution, and controlling the concentration of the gadolinium chloride solution to be 0.45mmol L-1Carrying out chelation reaction in a hydrothermal reaction kettle at 120 ℃;
6) and (3) carrying out rotary evaporation and freeze-drying treatment on the solution after the reaction to obtain Gd @ GQDs.
Performance tests were performed on Gd @ GQDs prepared in example 1.
FIG. 1 is a transmission electron microscope image of the Gd @ GQDs. It can be found that after gadolinium ions are added, GQDs have self-assembly behavior, and have the characteristics of large specific surface area, stable optical property, hydrophilic groups on the surface and the like.
FIG. 2 is a Fourier transform infrared spectrogram of Gd @ GQDs prepared by the invention. Wherein 3398cm-1Is the hydroxyl group stretching vibration peak, 2948cm-1Is a secondary amino group N-H stretching vibration peak, 1725cm-1Is C ═ O asymmetric stretching vibration peak, 1600cm-1The Gd @ GQDs prepared by the method have a large number of hydrophilic groups and simultaneously keep a certain graphene structure.
FIG. 3 shows the cytotoxicity of Gd @ GQDs prepared by MTT assay. The MTT method is a common method for detecting cell survival and growth, and the detection principle is as follows: succinate dehydrogenase in mitochondria of living cells can reduce exogenous MTT (thiazole blue) to water-insoluble blue-purple crystalline formazan to deposit in cells, dead cells do not have the function, then formazan in cells is dissolved out by DMSO (dimethyl sulfoxide), and absorbance is measured by an enzyme linked immunosorbent assay (ELISA) detector under the condition of 540nm or 720nm wavelength, so that the number of living cells is reflected by the indirect effect.
The results of the MTT cytotoxicity test show that: after human breast cancer cells (MCF-7) and Chinese hamster ovary Cells (CHO) (both provided by the institute of Life sciences of Anhui university) are co-cultured with Gd @ GQDs for 24 hours, the survival rate of the cells is still maintained above 90%, which indicates that the prepared Gd @ GQDs have very low toxicity.
FIG. 4 shows the r of Gd @ GQDs prepared by the invention in a 1.5T magnetic resonance testing system1And r2The relaxation rate indicates that Gd @ GQDs has extremely high r1The relaxation rate.
FIG. 5 shows Gd @ GQDs (0.2mg m L) prepared by the present invention-1，Gd3+The content of L is 0.2mmol-1) Graphene quantum dots (0.2mg m L)-1) Gadolinium chloride (0.2mmol L)-1) And Gd-DTPA (0.2mmol L)-1) T in 1.5T magnetic resonance test System after co-culture in MCF-7 cells, respectively1And the weighted magnetic resonance image shows that Gd @ GQDs have excellent contrast effect in the aspect of cell magnetic resonance imaging.
FIG. 6 shows that Gd @ GQDs of the present invention were used for cell fluorescence imaging, and the results show that MCF-7 cells did not fluoresce under a fluorescence microscope without the addition of Gd @ GQDs prepared in the present invention. After the Gd @ GQDs prepared by the invention is added, MCF-7 cells show blue fluorescence under a fluorescence microscope when excited by 405nm light, MCF-7 cells show green fluorescence under the fluorescence microscope when excited by 488nm light, and MCF-7 cells show red fluorescence under the fluorescence microscope when excited by 543nm light.
Example 2
A preparation method of a graphene quantum dot and gadolinium ion chelate specifically comprises the following steps:
1) preparing graphene oxide by using a Hummers method;
2) weighing 60mg of the graphene oxide, dissolving the graphene oxide in 60g of deionized water, treating with the ultrasonic power of 800W, and then adding 60g of the graphene oxide with the concentration of 1 mol. L-1The potassium persulfate solution is fully dissolved;
3) adding 800 mu L ammonia solution into the solution, transferring the solution into a round-bottom flask, and refluxing for 12 hours in an oil bath at 70 ℃;
4) after the reflux reaction is finished, carrying out chromatographic purification treatment on the solution to remove large-block impurities, and then carrying out freeze drying treatment to obtain GQDs;
5) the GQDs prepared above was formulated to a concentration of 0.2mg m L-1Then gadolinium chloride is added into the solution, and the concentration of the gadolinium chloride solution is controlled to be 0.2mmol L-1Carrying out chelation reaction at normal temperature;
6) dialyzing the solution after the reaction, and then drying at high temperature (100 ℃) to prepare Gd @ GQDs.
Example 3
A preparation method of a graphene quantum dot and gadolinium ion chelate specifically comprises the following steps:
1) preparing graphene oxide by using a Hummers method;
2) weighing 60mg of the graphene oxide, dissolving the graphene oxide in 60g of deionized water, treating with the ultrasonic power of 600W, and then adding 20g of mixed solution of concentrated sulfuric acid and concentrated nitric acid for full dissolution;
3) 400 mu L, 1mol L was added to the above solution-1Then transferring the solution into a round-bottom flask, and refluxing for 10 hours in an oil bath kettle at the temperature of 80 ℃;
4) after the reflux reaction is finished, carrying out suction filtration and purification treatment on the solution to remove large-block impurities, and then carrying out vacuum drying treatment to obtain GQDs;
5) the GQDs prepared above was formulated to a concentration of 0.05mg m L-1Then gadolinium chloride is added into the solution, and the concentration of the solution is controlled to be 0.1mmol L-1Carrying out chelation reaction in a water bath kettle at 60 ℃;
6) and distilling and drying the solution after the reaction to prepare Gd @ GQDs.
The graphene quantum dots prepared by the method and gadolinium ion chelates (Gd @ GQDs) are used according to the same operation steps of the commercial contrast agent. Can be used as magnetic resonance contrast agent and fluorescence imaging developer.
The Gd @ GQDs prepared by the method are easily dispersed in water, Phosphate Buffer Solution (PBS), biological culture medium and other aqueous solution systems; has good biocompatibility and low toxicity; in a 1.5T magnetic resonance test system, excellent T is shown1Weighted contrast performance of r1The relaxation rate is as high as 72mM-1s-1Compared with the prior commercial T1Weighting r of magnetic resonance contrast agent Gd-DTPA1The value is twenty times higher. In practical application, Gd in Gd @ GQDs3+The injection dosage of (A) is gadolinium-based T in the above-mentioned document1Contrast agents and general commercial gadolinium-based T1One fiftieth of the contrast agent. In addition, Gd in the Gd @ GQDs material of the invention3+Although only gadolinium-based T is present in the above-mentioned documents1Between one fourth and one third of the contrast agent, but still achieving a good magnetic resonance contrast, which makes Gd avoided from the source3+A large number of leakage hazards. The Gd @ GQDs can be used as a medical image developer and has good application prospect clinically.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (12)
1. The graphene quantum dot and gadolinium ion chelate is characterized in that the graphene quantum dot and gadolinium ion chelate are nano materials.
2. The method for preparing the chelate of the graphene quantum dot and the gadolinium ion according to claim 1, wherein graphene oxide is prepared by a Hummers method, and then the graphene oxide is heated and oxidized to obtain the graphene quantum dot, and finally the graphene quantum dot and Gd are mixed to obtain the graphene quantum dot3+And (4) chelating to form a stable graphene quantum dot and gadolinium ion chelate.
3. The preparation method of the graphene quantum dot and gadolinium ion chelate of claim 2, which is characterized by comprising the following steps:
1) preparing graphene oxide by using a Hummers method;
2) weighing the prepared graphene oxide, dissolving the graphene oxide in deionized water, carrying out ultrasonic treatment, and adding a certain amount of strong oxidant for full dissolution;
3) adding 400-1000 mu L alkali compound into the solution, and then refluxing for 7-12h at 70-120 ℃;
4) after the reflux is finished, purifying and drying to obtain graphene quantum dots;
5) preparing pure graphene quantum dots into a solution with a certain concentration, and then adding a certain amount of gadolinium chloride solution to perform chelation reaction under a certain condition;
6) and purifying and drying the solution after reaction to obtain the graphene quantum dot and gadolinium ion chelate.
4. The method for preparing the chelate of the graphene quantum dot and the gadolinium ion according to claim 3, wherein the ultrasonic power in the step 2) is 500-800W.
5. The method for preparing the chelate of the graphene quantum dot and the gadolinium ion according to claim 3, wherein the strong oxidant in the step 2) is one or more of potassium persulfate, hydrogen peroxide, concentrated sulfuric acid, concentrated nitric acid and hypochlorous acid.
6. The method for preparing the chelate of the graphene quantum dot and the gadolinium ion according to claim 3 or 5, wherein the mass ratio of the graphene oxide to the strong oxidant in the step 2) is (1-3): (1000-3000); the mass ratio of the graphene oxide to the deionized water is (1-3): (1000-3000).
7. The method for preparing the graphene quantum dot and gadolinium ion chelate according to claim 3, wherein the alkaline compound in step 3) is one or more of potassium hydroxide, sodium hydroxide, ammonia water, hydrazine hydrate, ethylenediamine and hydroxylamine.
8. The method for preparing the chelate of the graphene quantum dot and the gadolinium ion according to claim 3, wherein the purification in the steps 4) and 6) is any one or more of suction filtration, chromatography, dialysis, filtration, extraction and distillation fractionation; the drying in the step 4) and the step 6) is any one or more of vacuum drying, freeze drying and high-temperature drying.
9. The method for preparing the chelate of the graphene quantum dot and the gadolinium ion according to claim 3, wherein the concentration of the solution prepared from the graphene quantum dot in the step 5) is 0.05-0.4mg m L-1The concentration of the gadolinium chloride solution is 0.1-0.5mmol L-1。
10. The method for preparing the chelate of the graphene quantum dot and the gadolinium ion according to claim 3, wherein the chelation reaction in the step 5) is any one of water bath heating, hydrothermal reaction, solution dialysis and normal temperature treatment.
11. Use of the chelate according to claim 1 or the chelate of graphene quanta and gadolinium ions obtained by the preparation method according to any one of claims 2 to 10 as a developer for medical images.
12. The use of claim 11, wherein the medical image imaging agent comprises a magnetic resonance imaging contrast agent and a fluorescence imaging contrast agent.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910095524.6A CN111494649B (en) | 2019-01-31 | 2019-01-31 | Graphene quantum dot and gadolinium ion chelate magnetic resonance contrast agent and preparation method thereof |
| PCT/CN2019/076939 WO2020155286A1 (en) | 2019-01-31 | 2019-03-05 | Graphene quantum dot-gadolinium ion chelate magnetic resonance contrast agent and preparation method therefor |
| US17/422,211 US20220072161A1 (en) | 2019-01-31 | 2019-03-05 | Graphene quantum dots-gadolinium ion chelate as magnetic resonance imaging contrast agent and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910095524.6A CN111494649B (en) | 2019-01-31 | 2019-01-31 | Graphene quantum dot and gadolinium ion chelate magnetic resonance contrast agent and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111494649A true CN111494649A (en) | 2020-08-07 |
| CN111494649B CN111494649B (en) | 2021-11-12 |
Family
ID=71841560
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910095524.6A Active CN111494649B (en) | 2019-01-31 | 2019-01-31 | Graphene quantum dot and gadolinium ion chelate magnetic resonance contrast agent and preparation method thereof |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US20220072161A1 (en) |
| CN (1) | CN111494649B (en) |
| WO (1) | WO2020155286A1 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103330950A (en) * | 2013-06-17 | 2013-10-02 | 西安交通大学 | Method for preparing Gd3<+> magnetic resonance imaging contrast agent with graphene oxide serving as carrier |
| CN105797174A (en) * | 2016-01-22 | 2016-07-27 | 复旦大学附属肿瘤医院 | Nanometer graphene oxide-based magnetic resonance imaging contrast agent and preparation method thereof |
| WO2018080273A1 (en) * | 2016-10-31 | 2018-05-03 | 성균관대학교산학협력단 | Dna-peptide composite comprising high-density functional group, dna-peptide-nanomaterial composite and preparation method therefor, and dna-metal nanowire and manufacturing method therefor |
| WO2018093943A1 (en) * | 2016-11-16 | 2018-05-24 | The Regents Of The University Of California | Identification and optimization of carbon radicals on hydrated graphene oxide for ubiquitous antibacterial coatings |
| CN108619532A (en) * | 2018-05-22 | 2018-10-09 | 电子科技大学 | A kind of core-shell type nano drug and preparation method thereof for neoplasm in situ visualization treatment |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102397563B (en) * | 2010-09-16 | 2013-12-25 | 同济大学 | Preparation method for nanometer graphene carrier used for magnetic resonance imaging (MRI) contrast agent |
| US9887046B2 (en) * | 2012-12-28 | 2018-02-06 | Jiangnan University | Graphene composites and methods of making and using the same |
| CN103143361B (en) * | 2013-03-29 | 2014-12-03 | 北京化工大学 | Graphene-promoted hydrotalcite-based denitration catalyst and preparation method thereof |
| CN103708446B (en) * | 2013-12-27 | 2015-11-18 | 中国科学院上海微系统与信息技术研究所 | Graphene oxide quantum dot raw powder's production technology |
| CN106348281A (en) * | 2015-07-13 | 2017-01-25 | 南京理工大学 | Method for preparing bifluorescence graphene quantum dots hydrothermally |
-
2019
- 2019-01-31 CN CN201910095524.6A patent/CN111494649B/en active Active
- 2019-03-05 WO PCT/CN2019/076939 patent/WO2020155286A1/en active Application Filing
- 2019-03-05 US US17/422,211 patent/US20220072161A1/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103330950A (en) * | 2013-06-17 | 2013-10-02 | 西安交通大学 | Method for preparing Gd3<+> magnetic resonance imaging contrast agent with graphene oxide serving as carrier |
| CN105797174A (en) * | 2016-01-22 | 2016-07-27 | 复旦大学附属肿瘤医院 | Nanometer graphene oxide-based magnetic resonance imaging contrast agent and preparation method thereof |
| WO2018080273A1 (en) * | 2016-10-31 | 2018-05-03 | 성균관대학교산학협력단 | Dna-peptide composite comprising high-density functional group, dna-peptide-nanomaterial composite and preparation method therefor, and dna-metal nanowire and manufacturing method therefor |
| WO2018093943A1 (en) * | 2016-11-16 | 2018-05-24 | The Regents Of The University Of California | Identification and optimization of carbon radicals on hydrated graphene oxide for ubiquitous antibacterial coatings |
| CN108619532A (en) * | 2018-05-22 | 2018-10-09 | 电子科技大学 | A kind of core-shell type nano drug and preparation method thereof for neoplasm in situ visualization treatment |
Non-Patent Citations (3)
| Title |
|---|
| CHUN-LIN HUANG ET AL: "Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery", 《J. MATER. CHEM. B》 * |
| YUQI YANG ET AL: "Engineered Paramagnetic Graphene Quantum Dots with Enhanced Relaxivity for Tumor Imaging", 《NANO LETT.》 * |
| 史本照: "石墨烯量子点的功能化修饰及其在生物成像和药物传输中的应用", 《中国优秀硕士学位论文全文数据库工程科技I辑》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2020155286A1 (en) | 2020-08-06 |
| CN111494649B (en) | 2021-11-12 |
| US20220072161A1 (en) | 2022-03-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Dong et al. | Ultrasmall biomolecule-anchored hybrid GdVO 4 nanophosphors as a metabolizable multimodal bioimaging contrast agent | |
| Li et al. | An 800 nm driven NaErF 4@ NaLuF 4 upconversion platform for multimodality imaging and photodynamic therapy | |
| Yin et al. | Lanthanide-doped GdVO 4 upconversion nanophosphors with tunable emissions and their applications for biomedical imaging | |
| Liu et al. | Conjugation of NaGdF4 upconverting nanoparticles on silica nanospheres as contrast agents for multi-modality imaging | |
| Xiao et al. | Radiopaque fluorescence-transparent TaOx decorated upconversion nanophosphors for in vivo CT/MR/UCL trimodal imaging | |
| Wang et al. | Hydrothermal and biomineralization synthesis of a dual-modal nanoprobe for targeted near-infrared persistent luminescence and magnetic resonance imaging | |
| Ren et al. | Lanthanide ion-doped GdPO 4 nanorods with dual-modal bio-optical and magnetic resonance imaging properties | |
| Liao et al. | One-pot synthesis of gadolinium (III) doped carbon dots for fluorescence/magnetic resonance bimodal imaging | |
| AU579411B2 (en) | Gadolinium chelates as nmr contrast agents | |
| Yang et al. | Long-term in vivo biodistribution and toxicity of Gd (OH) 3 nanorods | |
| Mimun et al. | Bimodal imaging using neodymium doped gadolinium fluoride nanocrystals with near-infrared to near-infrared downconversion luminescence and magnetic resonance properties | |
| CN107955606B (en) | Double-rare-earth-doped carbon spot magnetic resonance/CT/fluorescence multi-mode imaging probe and preparation method thereof | |
| JP6608805B2 (en) | Contrast formulations and related preparation methods | |
| Wang et al. | Multi-functional NaErF 4: Yb nanorods: enhanced red upconversion emission, in vitro cell, in vivo X-ray, and T 2-weighted magnetic resonance imaging | |
| Yin et al. | Biocompatible folate-modified Gd 3+/Yb 3+-doped ZnO nanoparticles for dualmodal MRI/CT imaging | |
| Li et al. | Multifunctional BaYbF5: Gd/Er upconversion nanoparticles for in vivo tri-modal upconversion optical, X-ray computed tomography and magnetic resonance imaging | |
| Liu et al. | Mn-complex modified NaDyF 4: Yb@ NaLuF 4: Yb, Er@ polydopamine core–shell nanocomposites for multifunctional imaging-guided photothermal therapy | |
| Jiang et al. | Self‐Confirming Magnetosomes for Tumor‐Targeted T1/T2 Dual‐Mode MRI and MRI‐Guided Photothermal Therapy | |
| Liu et al. | Sequential growth of CaF 2: Yb, Er@ CaF 2: Gd nanoparticles for efficient magnetic resonance angiography and tumor diagnosis | |
| Huang et al. | Facile and large-scale synthesis of Gd (OH) 3 nanorods for MR imaging with low toxicity | |
| Li et al. | One-pot hydrothermal preparation of gadolinium-doped silicon nanoparticles as a dual-modal probe for multicolor fluorescence and magnetic resonance imaging | |
| Li et al. | Current progress in the controlled synthesis and biomedical applications of ultrasmall (< 10 nm) NaREF 4 nanoparticles | |
| CN104784711B (en) | The high relaxation rate gadolinium oxide magnetic resonance nano probe of stabilizing hyaluronic | |
| Zhang et al. | Core–shell BaYbF 5: Tm@ BaGdF 5: Yb, Tm nanocrystals for in vivo trimodal UCL/CT/MR imaging | |
| Cui et al. | A novel near-infrared nanomaterial with high quantum efficiency and its applications in real time in vivo imaging |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information |
Inventor after: Bi Hong Inventor after: Wang Dong Inventor before: Bi Hong Inventor before: Wang Dong |
|
| CB03 | Change of inventor or designer information |